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Multidimensional Omics Analysis in Malignant Pleural Mesothelioma (OMIM)

24 de abril de 2026 atualizado por: Azienda USL Reggio Emilia - IRCCS

Multidimensional Omics and Functional Approaches to Improve Immunotherapy Efficacy in Malignant Pleural Mesothelioma

Malignant pleural mesothelioma (MPM) is a rare and incurable cancer. Most patients are diagnosed with unresectable disease for which treatment options are limited. The lack of prognostic biomarkers further complicates the decision-making. Recently, the introduction of immune checkpoint inhibitors (ICIs) has marked a shift but has failed to produce significant benefits for a large proportion of patients. Maximizing the efficiency of ICIs and developing new protocols to improve drug efficacy is the best possible strategy for improving the life expectancy and quality of life of patients with MPM. This study aims to characterize the organization of the immune system infiltrating mesothelioma and the dynamics of its interaction with the tumor. The rationale is that deciphering this complexity will help improve our understanding of the mechanisms underlying this disease and provide a new tool to optimize the use of ICIs in these patients.

Visão geral do estudo

Status

Recrutamento

Condições

Mesotelioma Pleural Maligno (MPM)

Descrição detalhada

Malignant Pleural Mesothelioma (MPM) is a rare and highly aggressive malignancy characterized by poor prognosis and limited therapeutic options. Most patients are diagnosed at an advanced, unresectable stage, with a median overall survival of approximately one year. Although the introduction of immune checkpoint inhibitors (ICIs) has represented a significant advancement, a substantial proportion of patients fail to derive meaningful clinical benefit. The lack of reliable prognostic and predictive biomarkers, together with marked molecular heterogeneity and limited understanding of disease biology, significantly hampers the development of effective therapeutic strategies. MPM is strongly associated with chronic inflammation driven by asbestos exposure, which profoundly alters the pleural microenvironment. Within this context, tumor cells and immune cells engage in dynamic and reciprocal interactions, generating a complex ecosystem that promotes disease progression and the emergence of aggressive phenotypes. The ability of tumor cells to modulate immune system activity is considered a key driver of MPM pathogenesis. This study aims to comprehensively characterize the organization of the tumor-infiltrating immune system and the dynamic interactions between tumor and immune cells. To achieve this goal, an integrative and multidimensional omics approach will be employed to generate a high-resolution map of MPM ecosystem and to identify novel biomarkers and potential therapeutic targets. This is an exploratory, non-interventional, non-pharmacological study with both prospective and retrospective components, conducted exclusively on biological samples collected during routine clinical practice. The study population will be structured into three complementary cohorts. A training prospective cohort (C1 - Training Set) including newly diagnosed MPM patients from whom fresh frozen (FF) tumor samples will be collected from diagnostic biopsies, surgical resections, or malignant pleural effusions, enabling in-depth characterization of the tumor and immune microenvironment. A validation independent retrospective cohort (C2 - Validation Set) including MPM samples collected between 2015 and 2022 and used to validate findings obtained in the training cohort. A nested cohort within C1 (C3 - HITHOC Set) that will include patients undergoing surgery combined with hyperthermic intrathoracic chemotherapy (HITHOC), allowing investigation of tumor-immune interactions and treatment response mechanisms in this specific clinical setting. By integrating data across these three cohorts, the study aims to identify immune-related markers associated with tumor aggressiveness, discover novel targets for next-generation immunotherapies, and characterize mechanisms underlying response to chemotherapy, with particular focus on the HITHOC setting. Expected outcomes include improved understanding of MPM biology, identification of novel biomarkers, and optimization of immunotherapy strategies, ultimately contributing to the development of more effective and personalized treatments for patients affected by this disease.

Tipo de estudo

Observacional

Inscrição (Estimado)

300

Contactos e Locais

Esta seção fornece os detalhes de contato para aqueles que conduzem o estudo e informações sobre onde este estudo está sendo realizado.

Contato de estudo

Nome: Alessia Ciarrocchi, PhD
Número de telefone: 0522/295668
E-mail: alessia.ciarrocchi@ausl.re.it

Locais de estudo

Itália
- - Catania, Itália
    - Recrutamento
    - Azienda Ospedaliera Universitaria Policlinico Rodolico San Marco di Catania
    - Contato:
      
      Giacomo Cusumano, MD PhD
      
      Número de telefone: 095 3781175
      
      E-mail: giacomo.cusumano@unict.it
  - Naples, Itália
    - Recrutamento
    - Azienda Ospedaliera Universitaria Luigi Vanvitelli, Napoli
    - Contato:
      
      Alfonso Fiorelli, MD PhD
      
      E-mail: alfonso.fiorelli@unicampania.it
  - Reggio Emilia, Itália
    - Recrutamento
    - Azienda USL IRCCS di Reggio Emilia
    - Contato:
      
      Alessia Ciarrocchi, PhD
      
      Número de telefone: 0522/295668
      
      E-mail: alessia.ciarrocchi@ausl.re.it
    - Investigador principal:
      
      Alessia Ciarrocchi, PhD
  - Roma, Itália
    - Recrutamento
    - Fondazione Policlinico Universitario Agostino Gemelli IRCCS
    - Contato:
      
      Filippo Lococo, MD
      
      Número de telefone: 06 8881 8881
      
      E-mail: filippo.lococo@policlinicogemelli.it

Critérios de participação

Os pesquisadores procuram pessoas que se encaixem em uma determinada descrição, chamada de critérios de elegibilidade. Alguns exemplos desses critérios são a condição geral de saúde de uma pessoa ou tratamentos anteriores.

Critérios de elegibilidade

Idades elegíveis para estudo

Adulto
Adulto mais velho

Aceita Voluntários Saudáveis

Não

Método de amostragem

Amostra de Probabilidade

População do estudo

The study population includes patients diagnosed with Malignant Pleural Mesothelioma (MPM). Both prospective and retrospective cohorts will be included to ensure a comprehensive and biologically representative characterization of the disease. Eligible patients will have histologically confirmed MPM and available tumor biological samples obtained from diagnostic biopsies, surgical resections, or pleural effusions. Samples will include both fresh frozen (FF) material and formalin-fixed paraffin-embedded (FFPE) archival specimens.

Descrição

Inclusion Criteria:

Participant is willing and able to give informed consent for participation in the study
Aged > 18 years
Patients with histologically confirmed diagnosis of MPM
Availability of biological material
Clinical indicatio of eligibility for HITOCH protocol (only for C3 cohort)

Exclusion Criteria:

Active current infection
Autoimmune disease
Women in childbearing age not able to exclude pregnancy

Plano de estudo

Esta seção fornece detalhes do plano de estudo, incluindo como o estudo é projetado e o que o estudo está medindo.

Como o estudo é projetado?

Detalhes do projeto

Número de grupos/coortes

Coortes e Intervenções

Grupo / Coorte
C1 - Training set A prospective cohort of MPM patients enrolled. Analyses will be performed on fresh frozen (FF) tumor samples derived from diagnostic biopsies, surgical resections, or malignant pleural effusions (MPE).
C2 - Validation Set An independent retrospective cohort of MPM samples collected between 2015 and 2022. This cohort will serve to validate findings obtained in the training set.
C3 - HITHOC Set An prospective cohort of patients undergoing surgery combined with hyperthermic intrathoracic chemotherapy (HITHOC). This cohort will enable investigation of tumor-immune interactions and treatment response mechanisms in this specific clinical setting.

O que o estudo está medindo?

Medidas de resultados primários

Medida de resultado	Descrição da medida	Prazo
High-resolution mapping of the organization of the tumor-infiltrating immune system in MPM Prazo: 36 months	Characterization of the composition, functional state, and spatial organization of tumor-infiltrating immune cells using integrated bulk, single-cell, and spatial transcriptomic analyses on tumor tissues and malignant pleural effusions.	36 months

Medidas de resultados secundários

Medida de resultado	Prazo
Immune-related gene signatures by whole transcriptome sequencing (normalized counts). Prazo: 36 months	36 months
Immune-phenotyping by multiple parametric cytofluorimetry (cell counts) Prazo: 36 months	36 months
Analysis of circulating cytokines by bead-based multiplex assays (concentration micrograms/microliter) Prazo: 36 months	36 months
Association between immune features and clinical outcomes by correlation between gene expression (normalized, cell counts and/or concentration counts) and overall survival (months) Prazo: 36 months	36 months
Association between transcriptional signatures and pathological response to chemotherapy by correlation of gene expression (normalized counts) and response to therapy (time to progression -months) Prazo: 36 months	36 months

Colaboradores e Investigadores

É aqui que você encontrará pessoas e organizações envolvidas com este estudo.

Patrocinador

Azienda USL Reggio Emilia - IRCCS

Investigadores

Investigador principal: Alessia Ciarrocchi, Azienda USL - IRCCS di Reggio Emilia

Datas de registro do estudo

Essas datas acompanham o progresso do registro do estudo e os envios de resumo dos resultados para ClinicalTrials.gov. Os registros do estudo e os resultados relatados são revisados pela National Library of Medicine (NLM) para garantir que atendam aos padrões específicos de controle de qualidade antes de serem publicados no site público.

Datas Principais do Estudo

Início do estudo (Real)

30 de agosto de 2024

Conclusão Primária (Real)

30 de agosto de 2024

Conclusão do estudo (Estimado)

28 de fevereiro de 2027

Datas de inscrição no estudo

Enviado pela primeira vez

16 de abril de 2026

Enviado pela primeira vez que atendeu aos critérios de CQ

24 de abril de 2026

Primeira postagem (Real)

1 de maio de 2026

Atualizações de registro de estudo

Última Atualização Postada (Real)